Breast Cancer
Conditions
Keywords
recurrent breast cancer, stage IV breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as ABI-007(Nab-Paclitaxel((Nanoparticle Albumin Bound)-Paclitaxel)) and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving ABI-007 together with gemcitabine works in treating women with metastatic breast cancer.
Detailed description
OBJECTIVES: Primary * Determine the antitumor activity of ABI-007 and gemcitabine, in terms of response rate in women with metastatic breast cancer. * Determine the toxicity profile of this regimen, in terms of incidence and severity of observed toxic effects, in these patients. Secondary \* Determine the time to disease progression and survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive ABI-007 IV over 30 minutes and gemcitabine IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for up to 5 years. PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study within 20 months.
Interventions
DRUGGemcitabine
1000 mg/m2 (IV over 30 min) (days 1 and 8) on 21 day cycle
125 mg/m2 (IV over 30 min) (days 1 and 8) on 21 day cycle
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed invasive breast cancer \- Clinical evidence of metastatic disease \+ No bone metastases or other non-measurable disease as the only evidence of metastasis * Measurable disease, defined as at least 1 measurable lesion \- The following are considered non-measurable disease: * Small lesions (\< 2 cm) * Bone lesions * Leptomeningeal disease * Ascites * Pleural or pericardial effusions * Inflammatory breast disease * Lymphangitis cutis or pulmonis * Abdominal masses that are not confirmed and followed by imaging techniques * Cystic lesions * HER2(human epidermal growth factor receptor 2)-positive disease allowed provided patient has received prior treatment with trastuzumab * No evidence of active brain metastasis, including leptomeningeal involvement * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 18 and over Sex * Female Menopausal status * Not specified Performance status * ECOG 0-1 Life expectancy * At least 12 weeks Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9 g/dL Hepatic * AST and ALT ≤ 2.5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 times ULN Renal * Creatinine ≤ 1.5 mg/dL Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 30 days after completion of study treatment * No pre-existing peripheral neuropathy \> grade 1 * No other clinically significant illness or significant medical condition that would preclude study participation * No history of allergy or hypersensitivity to paclitaxel protein-bound particles in an injectable suspension, paclitaxel, gemcitabine, albumin, drug product excipients, or agents that are chemically similar to study drugs * No serious medical risk factors involving any of the major organ systems that would preclude study participation * No active stage III or IV invasive non-breast malignancy within the past 5 years PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics Chemotherapy * No more than 1 prior adjuvant chemotherapy regimen * No prior chemotherapy for metastatic disease * At least 6 months since prior adjuvant or neoadjuvant taxane * More than 2 weeks since prior cytotoxic chemotherapy * Prior neoadjuvant chemotherapy allowed * No other concurrent chemotherapy Endocrine therapy * Prior hormonal treatment as adjuvant therapy or for metastatic disease allowed Radiotherapy * Prior radiotherapy to target lesion allowed provided there is evidence of disease progression after completion of treatment * More than 2 weeks since prior radiotherapy, except radiotherapy to a non-target lesion only or single-dose palliative radiotherapy * No concurrent radiotherapy Surgery * Not specified Other * More than 2 weeks since prior investigational drugs * No concurrent participation in another clinical trial that is studying investigational procedures or therapies * Concurrent bisphosphonates (e.g., pamidronate or zoledronate) allowed for palliation of pain or lytic lesions from breast cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With Confirmed Responses | Two consecutive evaluations at least 6 weeks apart | Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 6 weeks apart. Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | Time from registration to progression or death (up to 5 years) | Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who are alive and progression free being censored on the date of their last evaluation. |
| Overall Survival | Death or last follow-up (up to 5 years) | Overall survival time was defined as the number of days from registration to the date of death or last follow-up |
| Adverse Event | Every 6 weeks | Number of patients that experienced adverse events (grade 3 or more occurring in \>5% of patients) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0 |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 22 medical clinics in the United States between November 2005 to May 2006
Participants by arm
| Arm | Count |
|---|---|
| Nab-paclitaxel/Gemcitabine Nab (nanoparticle albumin-bound)-Paclitaxel (125mg/m\^2)(IV over 30 min) (days 1 and 8) on 21 day cycle and gemcitabine (1000 mg/m\^2)(IV over 30 min) (days 1 and 8) on 21 day cycle | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 9 |
| Overall Study | Alternate Therapy | 5 |
| Overall Study | Death | 1 |
| Overall Study | Intercurrent Illness | 1 |
| Overall Study | Other | 2 |
| Overall Study | Patient Refusal | 10 |
Baseline characteristics
| Characteristic | Nab-paclitaxel/Gemcitabine |
|---|---|
| Age Continuous | 56 years |
| Dominant disease site Osseous | 4 participants |
| Dominant disease site Soft tissue | 5 participants |
| Dominant disease site Visceral | 41 participants |
| Estrogen receptor status Negative | 14 participants |
| Estrogen receptor status Positive | 34 participants |
| Estrogen receptor status Unknown | 2 participants |
| HER2 (human epidermal growth factor receptor 2) status Negative | 49 participants |
| HER2 (human epidermal growth factor receptor 2) status Positive | 1 participants |
| Number of metastatic sites 1 | 5 participants |
| Number of metastatic sites 2 | 15 participants |
| Number of metastatic sites 3+ | 30 participants |
| Performance Score 0 - Fully Active | 23 participants |
| Performance Score 1 - Ambulatory, restricted strenuous activity | 27 participants |
| Progesterone receptor status Negative | 20 participants |
| Progesterone receptor status Positive | 28 participants |
| Progesterone receptor status Unknown | 2 participants |
| Region of Enrollment United States | 50 participants |
| Sex/Gender, Customized Female | 50 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 50 |
| serious Total, serious adverse events | 11 / 50 |
Outcome results
Primary
Proportion of Patients With Confirmed Responses
Confirmed tumor response (complete and partial) as measured by RECIST(Response Evaluation Criteria In Solid Tumors) criteria on 2 consecutive evaluations at least 6 weeks apart. Confirmed tumor response is at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions.
Time frame: Two consecutive evaluations at least 6 weeks apart
Population: per protocol
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nab-paclitaxel/Gemcitabine | Proportion of Patients With Confirmed Responses | Confirmed response | 25 participants |
| Nab-paclitaxel/Gemcitabine | Proportion of Patients With Confirmed Responses | Assessable | 50 participants |
Comparison: Proportion of confirmed responses was estimated by the number of patients who achieved a confirmed response divided by the total number of assessable patients.95% CI: [36, 64]
Secondary
Adverse Event
Number of patients that experienced adverse events (grade 3 or more occurring in \>5% of patients) as measured by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0
Time frame: Every 6 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nab-paclitaxel/Gemcitabine | Adverse Event | Neutropenia | 27 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Fatigue | 14 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Anemia | 7 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Dyspnea | 7 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Thrombocytopenia | 6 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Arthralgia | 4 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Vomiting | 4 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Neuropathy | 3 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Myalgia | 3 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Nausea | 3 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Pain-abdominal | 3 participants |
| Nab-paclitaxel/Gemcitabine | Adverse Event | Aspartate aminotransferase (AST) | 3 participants |
Secondary
Overall Survival
Overall survival time was defined as the number of days from registration to the date of death or last follow-up
Time frame: Death or last follow-up (up to 5 years)
Population: Median survival time from Kaplan-meir estimate has not been attained.
Secondary
Progression-free Survival
Progression-free survival was defined as the number of months from registration to the date of disease progression or death, with patients who are alive and progression free being censored on the date of their last evaluation.
Time frame: Time from registration to progression or death (up to 5 years)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nab-paclitaxel/Gemcitabine | Progression-free Survival | 7.9 months |